The metabolic challenges present in tumors attenuate the metabolic fitness and antitumor activity of tumor-infiltrating T lymphocytes (TILs). However, it remains unclear whether persistent metabolic ...insufficiency can imprint permanent T cell dysfunction. We found that TILs accumulated depolarized mitochondria as a result of decreased mitophagy activity and displayed functional, transcriptomic and epigenetic characteristics of terminally exhausted T cells. Mechanistically, reduced mitochondrial fitness in TILs was induced by the coordination of T cell receptor stimulation, microenvironmental stressors and PD-1 signaling. Enforced accumulation of depolarized mitochondria with pharmacological inhibitors induced epigenetic reprogramming toward terminal exhaustion, indicating that mitochondrial deregulation caused T cell exhaustion. Furthermore, supplementation with nicotinamide riboside enhanced T cell mitochondrial fitness and improved responsiveness to anti-PD-1 treatment. Together, our results reveal insights into how mitochondrial dynamics and quality orchestrate T cell antitumor responses and commitment to the exhaustion program.
Combination therapy has attracted extensive interest in alleviating the shortcomings of monotherapy and enhancing the treatment efficacy. In this work, hollow mesoporous silica nanoparticles (HMSNs) ...play the role of nanocarriers in the delivery of Cu(II)-doped polydopamine (PDA), termed as HMSNs@PDA-Cu, for synergistic therapy. PDA acts as a traditional photothermal agent to realize photothermal treatment (PTT). Chemodynamic therapy (CDT) is realized by the reaction of Cu(II) with intracellular glutathione (GSH), and subsequently, the generated Cu(I) reacts with H2O2 to produce toxic hydroxyl radical (•OH) through a Fenton-like reaction. The photothermal performance of PDA is improved after its coordination with Cu(II). On the other hand, PDA exhibits superoxide dismutase (SOD)-mimicking activity. PDA converts O2 •– to H2O2 and improves the production of H2O2, which promotes the therapeutic effect of CDT. Moreover, the high temperature caused by PTT further enhances the yield of •OH for CDT. This nanotheranostic platform perfectly applied to the tumor depletion of mice, presenting great potential for cancer metastasis therapy in vitro and in vivo.
Various multi-drug-resistant microorganisms have appeared while a single antibacterial agent is increasingly no longer adequate for dealing with these resistant microorganisms. Herein, commercially ...purchased 50 nm-average-diameter silver nanoparticles (AgNPs) and Lactobacillus buchneri-isolated surface-layer proteins (SLPs) as a capping agent were used to fabricate a hybrid antibacterial agent (SLP-AgNPs) with enhanced antibacterial activity, and the possible synergistic antibacterial mechanism was explored. Characterization results revealed that SLP-AgNPs were uniformly surrounded by protein corona provided from SLP, and the formulations were mainly mediated by the electrostatic interactions and hydrogen bonding, which was evidenced by the results of Fourier transform infrared spectroscopy. According to the antibacterial tests, the minimum inhibitory concentration of SLP-AgNPs against Salmonella enterica (0.010 mg/mL) and Staphylococcus aureus (0.005 mg/mL) was 5–10 times lower than that of bare AgNPs, and while SLP-AgNPs showed a higher antibiofilm activity. Furthermore, bacterial cells exposed to SLP-AgNPs exhibited higher cell membrane permeability and stronger inhibition of respiratory-chain dehydrogenase activity, resulting in more severe cell death compared with bare AgNPs. The synergistic effect of SLP on AgNPs was probably carried out by enhanced function of adhesion to bacteria and antibacterial ability of SLP and SLP’s supramolecular lattice structure on the sustained release of silver ion.
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•The SLPs from Lactobacillus buchneri were extracted and purified.•The hybrid antibacterial agent SLP-AgNPs were fabricated and characterized.•The self-assembly property of SLP contributed to the synthesis of SLP-AgNPs.•The modification of SLP resulted in enhanced antibacterial activities of AgNPs.•The synergy of SLP on AgNPs relied on the function of SLP and SLP lattice.
Chemodynamic therapy (CDT) is a new emerging strategy for the in situ treatment of tumors. In the microenvironment of tumor cells, CDT may be achieved through the generation of reactive oxygen ...species (ROS), e.g., hydroxyl radicals (˙OH) and singlet oxygen (
O
), which induce the death of tumor cells. Copper (Cu) or other transition-metal ions catalyze the production of ˙OH by hydrogen peroxide (H
O
) through Fenton or Fenton-like reactions. With the development of advanced nanotechnology, nanotherapeutic systems with Cu-based nanostructures have received extensive attention and have been demonstrated for their wide applications in the design and construction of nanotherapeutic systems for CDT, along with multimodal synergistic therapy. Herein, the cutting-edge developments of Cu-based nanostructures in CDT are reviewed and discussed, by focusing on the monotherapy of CDT as well as synergistic treatments by hyphenating CDT with various therapeutic protocols, e.g., photothermal therapy (PTT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and so on. In addition, the potential challenges and future perspectives are described in the improvement of CDT therapeutic efficacy, the enhancement of targeting capability, and mechanistic investigations on CDT therapy.
With the deepening of the concept of recycling economy and green chemistry, selective capture of Cu(II) from wastewater by biosorbent and reuse of the spent Cu(II)-loaded adsorbent are of great ...significance. Herein, we synthesized composite of rice husk (RH) with mesoporous silica MCM-41 (RH@MCM-41) modified by organosilane containing amino and schiff groups as functional monomer and cross-linking agent. The silica modified RH@MCM-41 was employed as supporter to fabricate copper ion-imprinted polymers as absorbents (named as RM-CIIPs) via surface ion imprinting technique. Adsorption isotherms, kinetics, selectivity and mechanism of RM-CIIPs to remove Cu(II) were investigated with respect to different adsorption condition. Furthermore, we explored the catalytic activity of spent Cu(II)-loaded adsorbent in Glaser coupling reaction. Batch adsorption studies revealed that RM-CIIP-3 prepared with functional monomer shows the best adsorption capacity (91.4 mg/g) for Cu(II), and adsorption equilibrium could be reached within 30 min. RM-CIIP-3 exhibited an excellent selectivity for capturing Cu(II) and reusability in six adsorption/desorption cycles. More importantly, the spent Cu(II)-loaded adsorbent could be used as bio-heterogeneous catalyst and afford the desired product (1,4-diphenylbutadiyne) in 99.1% yield. Our research indicates an eco-friendly systematic strategy to utilize the waste material as an adsorbent for removing heavy metals and catalyst for industry.
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•The rice husk-based ion imprinted polymer adsorbent was developed.•The RM-CIIP-3 exhibits excellent adsorption capacity and selectivity for Cu(II).•The OCASBG was employed as functional monomer and cross-linking agent.•RM-CIIP-3-Cu was first time used as a bio-heterogeneous catalyst in Glaser coupling.
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•Zijuan tea kombucha with attractive color, salmon-pink, is infrequent in kombucha.•Its anthocyanins with pH-responsiveness of color change led to the salmon-pink color.•Zijuan tea ...kombucha showed the highest overall acceptability score among all samples.•Zijuan tea kombucha presented the highest antioxidant activity among all samples.
Zijuan tea is a representative anthocyanin-rich tea cultivar in China. In this study, Zijuan tea was used to produce a novel kombucha beverage (ZTK). The physicochemical, sensory properties, and antioxidant activity of ZTK were compared with that of black tea kombucha (BTK) and green tea kombucha (GTK). Results indicated that after fermentation, the color of ZTK changed from yellowish-brown to salmon-pink, because its anthocyanins (4.5 mg/L) appeared red in acidic conditions. Meanwhile no significant changes of color were observed in BTK and GTK. The dynamic changes of pH, biomass, and concentrations of sugars, amino acids, and main organic acids were similar in three kombucha beverages, except catechins showing different trends. Moreover, ZTK showed the highest overall acceptability score, antioxidant activity, and concentration of volatiles among the three kombucha beverages. Therefore, Zijuan tea is suitable for the preparation of kombucha beverage with attractive color and health benefits.
Illicit drug use has long been a key issue of international concern, and the true situation is unknown to the relevant authorities. To develop a profile of comprehensive consumption patterns of ...illicit drugs in China, data from 34 wastewater treatment plants in 25 cities were collected to analyze four classes of drugs, including amphetamine-type stimulants, opioids, ketamine, and cocaine. They were identified and quantified in samples using methods based on gas chromatography coupled to mass spectrometry. According to the wastewater-based epidemiology (WBE) approach, an analysis of the consumption pattern was performed regarding per inhabitant consumption based on the revised metabolic rate. The consumption quantity of illicit drug and precursor was divided into four categories based on statistical difference analyses: methamphetamine and ephedrine (precursor) were the predominant drugs in the first category, followed by ketamine and heroin in the second category, methcathinone and 3,4-methylenedioxymethamphetamine (MDMA) in the third category, and cocaine and methadone in the fourth category. There were distinctive spatial patterns: heroin and cocaine consumption was higher in Southern China than in Northern China, heroin consumption was higher in Western China than in Eastern China, and the consumption of each drug differed across seven regions of China, especially with ephedrine and methcathinone consumption higher in North China; heroin consumption higher in Southwest, Central, and Northwest China; and ketamine and MDMA consumption higher in East, South, and Central China. Compared with findings in previous studies, there were temporal patterns, in which ketamine consumption presented a downward trend but heroin remained stable. Based on correlation analyses, there were the polydrug abuse patterns between heroin and cocaine, methcathinone and ketamine, and cocaine and MDMA. In general, this study based on WBE provides a comprehensive evaluation of drug consumption in China.
Graphical abstract
An ultrasmall chemodynamic therapeutic (CDT) agent with favorable specificity to tumor microenvironment, i.e., high level of glutathione (GSH) and hydrogen peroxide (H2O2), is reported. The ...coordination polymer nanodot between divalent copper (Cu2+) and gallic acid (GA) is shortly named as Cu–GA. The ultrasmall size of Cu–GA (2.16 ± 0.3 nm) results in a large specific surface area, which is beneficial for improving its catalytic performance. After endocytosis into tumor cell interior, Cu–GA promotes GSH‐activated and H2O2‐reinforced CDT in situ, wherein divalent Cu(II) is reduced to monovalent Cu(I) by GSH and induced GSH depletion. Subsequently, the generated Cu(I) catalyzes local H2O2 to generate toxic hydroxyl radical (•OH) via Fenton‐like reaction, and •OH leads to tumor cell apoptosis. The higher levels of GSH and H2O2 in the tumor cell interior significantly improve the efficiency of CDT, and meanwhile protect the normal cells. In addition, the ultrasmall size of Cu–GA facilitates its fast clearance and eliminates long‐term body retention, with minimized systemic toxicity during the treatment in vivo. Therefore, as a novel copper‐based nanoformulation specifically responsive to the tumor microenvironment, Cu–GA provides promising potentials in CDT.
An ultrasmall polymer nanodot (Cu–GA, 2.16 ± 0.3 nm) is prepared through coordination between divalent copper (Cu2+) and gallic acid (GA). After endocytosis into tumor cell interior, divalent Cu(II) in Cu–GA is reduced to monovalent Cu(I) by glutathione and induced glutathione depletion. Cu(I)–GA subsequently catalyzes intracellular H2O2 to produce •OH to kill tumor cells.
In the past few years, ionic liquids (ILs)-based gels (gels contain ILs) have become a research hotspot. ILs-based gels combine the properties of gels with intrinsic ILs properties. According to the ...existence form and function of the ILs in the gel, the ILs-based gels are divided into three types. One is ILs hydrogels which the PILs, ILs polymerized into poly-ionic liquids, copolymerized with other polymers served as the continuous phase in the gel system. This type of gel can usually absorb water and is an ILs hydrogel. The other is ionic gels that are usually synthesized by high-molecular organic polymers as spatial network structure and ILs as a dispersed phase, which maintained the good performance of ILs. The third one is that the ILs acts as both the continuous phase and the dispersed phase of the gels. In all research fields, the pursuit of new materials aims at functional materials, which enhances specific and efficiency, and ultimately applications. The application of ILs-based gels ranges from energy storage, sensing, electrochemical devices, to antibacterial and gas capture. Different synthesis methods have different performances and applications of ILs-based gels. The purpose of this review is to provide the latest developments on ILs-based gels, perspectives on several applications, and some challenges that need to be aware of in this field.
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•Reviewed the preparation and properties of IL-based gels.•Highlighted the application of IL-based gels in the field of energy storage and sensors.•Discussed the existence form of ILs in gels.
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Home range and habitat use are the central components of avian ecology, and studies on these aspects will be helpful for the conservation and management of avian populations. Sixty‐seven swans were ...global positioning system tagged at Sanmenxia Wetland of Henan Province to obtain detailed location data in winter from 2015 to 2016. The home range size of swans was the largest in the middle wintering period and followed by the early period and late period, and sizes were significantly different among the three wintering periods. There were significant differences in habitat use among the different wintering periods. In the early period, the swans mainly used the aquatic grasses and emergent plants zones, and they mainly relied on artificial supplementation because of a lack of natural feeding habitats in the middle period. In the late period, the swans mainly used the newly emerged terrestrial grasses zone. Except for the deep water, the use of other water levels was significantly different among the different wintering periods. In the early wintering period, the swans tended to prefer the low and high water level areas; in the middle period, they were mainly in the intermediate and high water level areas and they used all the water level areas except the deep water level in the late wintering period. It was concluded that some plants are preferred by the swans, such as reeds, cattails and barnyard grass, and that water depth should be suitable for the swans, with the water levels varying over a gradient.
The main findings of this study were that the core area and home range size of the whooper swan significantly differed among the early, middle and late wintering periods, and there were also significant differences in swans use of natural emergent plants zone, introduced emergent plants zone, terrestrial grasses zone and aquatic plants zone among the different periods, and there were significant differences in swan use of low, intermediate and high water levels among the different periods while there was no significant difference among periods in the use of deep water level.
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